Synthesis and anti-HCV activity of β-D-2′-deoxy-2′-α-chloro-2′-β-fluoro and β-D-2′-deoxy-2′-α-bromo-2′-β-fluoro nucleosides and their phosphoramidate prodrugs

We report herein the synthesis and evaluation of a series of beta-D-2'-deoxy-2'-alpha-chloro-2'-beta-fluoro and beta-D-2'deoxy-2'-alpha-bromo-2'-beta-fluoro nucleosides along with their corresponding phosphoramidate prodrugs. Key intermediates, lactols 11 and 12, were obtained by a diastereoselective fluorination of protected 2-deoxy-2chloro/bromo-ribonolactones 7 and 8. All synthesized nucleosides and prodrugs were evaluated with a hepatitis C virus (HCV) subgenomic replicon system.